Journal of Neurology & Stroke Review Article Open Access Subplate neurons: their biopsychosocial role in cognitive and neurodevelopmental disorders, nociception and stress Abstract Volume 10 Issue 5 - 2020 A systematic review was carried out of the literature especially in humans reporting Rosana Maria Tristão, Andressa Carvalho the origin, functions and neural changes of the subplate zone and the relationships with neurodevelopmental disorders and stress or nociceptive reaction in neonates. Thirty-two Oliveira, Nágelin Ferreira Barreto, Carlos articles with established criteria were identified. Academic Google, SciElo, PubMed, Nogueira Aucélio, Geraldo Magela Scopus, Cochraine Library and Web of Science databases were searched until January Fernandes, Karina Nascimento Costa, José 2020 for scientific papers written in any language. Subplate neurons are present during Alfredo Lacerda de Jesus embryogenesis of the nervous system and shortly after birth. Through them, the brain University of Brasilia, Medicine of Child and Adolescent Area, forms the first connections between the thalamus and the cortex originating sensory and Brazil cognitive capacities. Because of this, disorders involving migration and apoptosis failures or tissue injury can lead to psychiatric disorders, such as autism and schizophrenia, and to Correspondence: Rosana Maria Tristão, Child and Adolescent morphological alterations that may alter cognitive functions, modify the perception of pain Area, Faculty of Medicine, University of Brasília, Darcy Ribeiro Campus, 70910-900, Phone +5561999689359, Brasília DF, Brazil, in fetuses and neonates and have repercussions in adult life. Accumulative evidences reveal Email the importance of subplate neurons for neurodevelopment, previously ignored because they are transient cells. The elucidation of some morphological aspects of the cerebral cortex Received: May 28, 2020 | Published: September 08, 2020 may explain mental disorders, the beginning of the perception of nociceptive stimuli and their implication in the long term. Keywords: subplate neurons, neonate, nociception, stress, cognition, neurodevelopmental disorder Introduction and the later development of events such as mental or neuropathic pain disorders. These SPNs mechanisms may also include links to During embryonic development in mammals a primordial group other disorders as mental retardation, autism and schizophrenia, as of neurons forms as one of the earliest circuits to integrate the cortex, well as the intricate pathways to the perception of pain in newborns called subplate neurons (SPN), which play an important role for and during adulthood.2–4 brain development and plasticity. Research aimed at understanding their functions is relatively recent, but studies have been carried out Methods to clarify their implications for neuronal development, as well as the relationship between brain lesions and the origin of some cases The search for articles was conducted in January 2020 in six of neurological disorders, namely autism and schizophrenia.1 In databases: Academic Google, PubMed, SciElo, Cochrane Library, addition, the better comprehension of the relationship between SPN- Scopus and Web of Science. The keywords used in all databases mediated connections and peripheral pathways may elucidate intricate were: “subplate neurons”, “newborn or neonate and subplate questions about the origins of high-level mental functions and the neuron”, “neurodevelopment disorder and subplate neurons”, roots for further disorders. “cognition and subplate neurons”, “stress and subplate neurons”, “pain or nociception and subplate neurons”, “Autism and subplate For instance, the origins of post-traumatic stress disorder symptoms neurons”, “Schizophrenia and subplate neurons”. Each combination in former premature children and adults may be possibly explained by corresponded to an individual query. Keywords had to appear in the the impact of stress reaction to nociceptive stimuli in the early brain, title or abstract. No restrictions were placed on language or year of fetuses and neonates, and its other long-term effects. This mechanism publication. The inclusion criteria for this review covered original is still poorly understood because it is unknown when the activity of articles and review articles explaining the formation, functions, and a primary consciousness begins in humans. Despite this, it is believed changes related to the SPN. Exclusion criteria were studies that did that the trigger for pain sensitivity occurs ahead of other senses, early not address SPN and cognition, neurodevelopmental disorder, mental and gradually, and not due to a single initiating event.1–3 It is known retardation, autism, pain, nociception, schizophrenia or stress. Thus, that for the perception of a painful stimulus it is necessary to have a 566 of the 623 previously chosen articles were excluded (Figure 1) connection between the nociceptors and the thalamic pathways and mainly for reasons as animal study, only physiologic analyses, not from there to the regions of the anterior insula, rotation of the anterior newborn infant or other reasons as oral/poster presentation only. cingulate and prefrontal cortex. Thus, it is relevant to discover at Reporting of the results followed the Preferred Reporting Items of what point in fetal development these structures are functional and Systematic reviews and Meta-Analyses (PRISMA) statement of 2009. communicating and which are related to alterations involving SPN Submit Manuscript | http://medcraveonline.com J Neurol Stroke. 2020;10(5):158‒164. 158 ©2020 Tristão et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Copyright: Subplate neurons: their biopsychosocial role in cognitive and neurodevelopmental disorders, nociception 159 and stress ©2020 Tristão et al. Results by the presence of cortical neurons that begin to migrate to the surface of the pia mater, forming a dense cortical plate. This, together with What are the SPN? the marginal zone (above the first) and the zone of the pre-subplate The development of the human cortex is a complex and gradual (below it), form a trilaminar structure that constitutes the initial fetal process involving distinct cells and lasts for years after birth until cortex. As the neurons of these regions are only beginning their it becomes fully functional. In general, it is possible to delineate development, there are still no thalamo-cortical connections or even subplate performance, which only has the generation of spontaneous three stages in cortical development: initial fetal circuit, transient 7,8 and the cortical circuit (permanent).5,6 During the formation of circuits and advanced morphological differentiation. The SPZ the telencephalon compartment, the subplate zone (SPZ), which begins to develop between 15 and 17 weeks of gestation, even when characterizes the said transient circuit, is of substantial relevance, axons from the basal forebrain and thalamus are developing, which above all due to the performance of SPNs, which appear to contribute seems to be important for the analysis of intrauterine disturbances that considerably to the maturation of this brain region by mediating may cause damage to cortical development. In this phase, synaptic and various events.1,4,6–9 non-synaptic contacts occur between glutamatergic and GABAergic neurons, which together with the so-called Cajal-Retzius cells initiate The SPZ is composed of migrating neurons, post-migratory functional activity in the cortex.8 neurons, glial cells, axons, dendrites and synapses, and is therefore composed of a reasonably heterogeneous cell population. The SPZ At around halfway through the gestational period, the SPZ is does not allow the use of a single molecular marker by fibrillary already well developed, being four times thicker than the cortical zone and, therefore, capable of being responsible for the formation elements (axons, dendrites), as well as a vast extracellular space 5,7 filled with a hydrophilic matrix.6–8 The SPZ constitutes a wall in the of synapses, with the presence of well-differentiated cells. In this fetal telencephalon and is extremely important both for structure phase, the subplate receives the arrival of additional neurons, which is and for intra- and extracortical connectivity.8 SPNs are located at the especially important for the development of the human brain, because white matter by permeating the cortical regions and allow synapse it allows the installation of cells with varied types and forms. It is also intensities to be lower than in the upper immature areas. They exist here that the second class of interstitial neurons found in adults appears, in an average number of 1.230 (+/- 549) in 1 mm3 of the subcortical which are located in the deep part of the periventricular white matter. white matter with the lowest number consistently observed in the Thus, as fetal development continues, the SPZ becomes the main limbic cortex, and the highest number in the frontal cortex.10 In post-synaptic target for all afferent systems in the cortex, receiving the SPZ there are also neurons that secrete glutamate (projection afferents from the basal forebrain, brainstem, thalamus, developing neurons), GABA (interneurons that act locally), and neurons that are corpus callosum and other regions. Neural connectivity encompasses receptors for acetylcholine and glycine, as well